title: Different drug-resistant influenza A(H3N2) variants in two immunocompromised patients treated with oseltamivir during the 2011-2012 influenza season in Italy.
abstract: BACKGROUND
  Monitoring the emergence of drug-resistant influenza variants is crucial in influenza surveillance programs.
  
  
  OBJECTIVE
  Influenza A kinetics and the emergence of drug-resistant strains in hospitalized patients treated with oseltamivir were investigated.
  
  
  METHODS
  Sequential samples from oseltamivir-treated and -untreated hospitalized patients in the period November 2011 through April 2012 were analyzed. NA gene was sequenced in samples from oseltamivir treated patients. Clonal analysis of the viral population was performed in patients unresponsive to treatment. Viral kinetics was determined in 24 (14 immunocompromised and 10 immunocompetent) A(H3N2)-positive patients treated and 24 (10 immunocompromised and 14 immunocompetent) untreated patients.
  
  
  RESULTS
  Viral shedding was significantly reduced in treated vs untreated immunocompromised patients (7 vs 22 days, p<0.05, respectively). Viral load decreased significantly in immunocompromised and immunocompetent treated patients as compared with immunocompromised and immunocompetent untreated patients (0.73 and 0.93 vs 0.47 and 0.45 log10/day, p<0.05). In two (8.3%) treated patients with prolonged virus shedding, the oseltamivir resistance R292K mutation was revealed. In these patients, clonal analysis of the virus population showed the presence of additional oseltamivir-resistant mutants (E119V, N294S and deletion Del247-250).
  
  
  CONCLUSIONS
  Oseltamivir resistance is reported for the first time in A(H3N2) virus strains during the 2011-2012 influenza season. Different drug-resistant viruses emerged in hospitalized immunocompromised patients showing prolonged virus shedding.
authors.affiliation: S.S. Virologia Molecolare, S.C. Virologia e Microbiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Piralla
authors.forename: M
authors.initials: M
authors.lastname: Gozalo-Margüello
authors.forename: L
authors.initials: L
authors.lastname: Fiorina
authors.forename: F
authors.initials: F
authors.lastname: Rovida
authors.forename: A
authors.initials: A
authors.lastname: Muzzi
authors.forename: A A
authors.initials: AA
authors.lastname: Colombo
authors.forename: P E
authors.initials: PE
authors.lastname: Alessandrino
authors.forename: F
authors.initials: F
authors.lastname: Baldanti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D053122:Influenza A Virus, H3N2 Subtype / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology*; D007558:Italy; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics; D053139:Oseltamivir / Q000627:therapeutic use*; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D014764:Viral Proteins; D053139:Oseltamivir; C487630:NA protein, influenza A virus; D009439:Neuraminidase
keywords: Del247–250; E119V; Influenza; N294S; Oseltamivir treated patients; R292K